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1.  Strategies to reduce pulmonary complications after esophagectomy 
Esophagectomy, the surgical removal of all or part of the esophagus, is a surgical procedure that is associated with high morbidity and mortality. Pulmonary complications are an especially important postoperative problem. Therefore, many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice. Here, we review these strategies, including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years. Furthermore, interventions such as methylprednisolone, neutrophil elastase inhibitor and epidural analgesia, which have been shown to reduce pulmonary complications, are discussed. Benefits of the commonly applied routine nasogastric decompression, delay of oral intake and prophylactic mechanical ventilation are unclear, and many of these strategies are also evaluated here. Finally, we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.
doi:10.3748/wjg.v19.i39.6509
PMCID: PMC3801361  PMID: 24151374
Esophagectomy; Complications; Pneumonia; Acute lung injury; Acute respiratory distress syndrome
2.  Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial) 
BMC Cancer  2015;15:556.
Background
For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy.
Methods
The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness.
Discussion
In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient.
Trial registration
NCT02248519
doi:10.1186/s12885-015-1551-z
PMCID: PMC4518687  PMID: 26219670
Gastric cancer; Gastrectomy; Laparoscopy
3.  Radiation dose does not influence anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation and transhiatal esophagectomy 
Background
Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to determine the influence of radiation dose on the incidence of leakage and stenosis.
Methods
Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis.
Results
Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis.
Conclusions
A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy.
doi:10.1186/s13014-015-0361-4
PMCID: PMC4369843  PMID: 25884226
Radiation dose; Anastomotic complications; Esophageal cancer
4.  The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery (SANICS II trial): a study protocol for a double-blind randomized controlled trial 
Trials  2015;16:20.
Background
Postoperative ileus and anastomotic leakage are important complications following colorectal surgery associated with short-term morbidity and mortality. Previous experimental and preclinical studies have shown that a short intervention with enriched enteral nutrition dampens inflammation via stimulation of the autonomic nervous system and thereby reduces postoperative ileus. Furthermore, early administration of enteral nutrition reduced anastomotic leakage. This study will investigate the effect of nutritional stimulation of the autonomic nervous system just before, during and early after colorectal surgery on inflammation, postoperative ileus and anastomotic leakage.
Methods/Design
This multicenter, prospective, double-blind, randomized controlled trial will include 280 patients undergoing colorectal surgery. All patients will receive a selfmigrating nasojejunal tube that will be connected to a specially designed blinded tubing system. Patients will be allocated either to the intervention group, receiving perioperative nutrition, or to the control group, receiving no nutrition. The primary endpoint is postoperative ileus. Secondary endpoints include anastomotic leakage, local and systemic inflammation, (aspiration) pneumonia, surgical complications classified according to Clavien-Dindo, quality of life, gut barrier integrity and time until functional recovery. Furthermore, a cost-effectiveness analysis will be performed.
Discussion
Activation of the autonomic nervous system via perioperative enteral feeding is expected to dampen the local and systemic inflammatory response. Consequently, postoperative ileus will be reduced as well as anastomotic leakage. The present study is the first to investigate the effects of enriched nutrition given shortly before, during and after surgery in a clinical setting.
Trial registration
ClinicalTrials.gov: NCT02175979 - date of registration: 25 June 2014.
Dutch Trial Registry: NTR4670 - date of registration: 1 August 2014.
doi:10.1186/s13063-014-0532-x
PMCID: PMC4318130  PMID: 25623276
Perioperative nutrition; Colorectal surgery; Postoperative ileus; Anastomotic leakage; Autonomic nervous system; Inflammation
5.  Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial 
Trials  2012;13:7.
Background
Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice.
Methods/Design
The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs.
Discussion
The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients.
Trial Registration
Netherlands Trial Register (NTR): NTR2666
doi:10.1186/1745-6215-13-7
PMCID: PMC3285056  PMID: 22236534
Acute cholecystitis; laparoscopic cholecystectomy; percutaneous cholecystostomy; percutaneous drainage
6.  Neoadjuvant radiotherapy of primary irresectable unicentric Castleman's disease: a case report and review of the literature 
Background
Castleman disease (CD) is a rare benign disorder characterised by hyperplasia of lymphoid tissue that may develop at a single site or throughout the body. The etiology of this disorder is unclear, although the histopathological presentation can be differentiated into a hyaline vascular variant, a plasma cell variant and a mixed variant. Clinically, it has been recorded that 3 manifestations of CD are characterized: a localized unicentric type, a generalized multicentric type and a mixed form. Surgery remains the main treatment for resectable unicentric CD, since removal of the large node is possible without further complications. No consensus has been reached concerning the most adequate treatment for irresectable unicentric CD.
Methods
Case report of a 67 year old woman.
Results
This report, describes the case of a 67-year-old woman with unicentric Castleman disease located in the right lower abdomen. The patient had symptoms of fatigue, dyspnoea and pain in the right lower abdomen. Computed tomography (CT)- examination revealed a tumour, which had grown to form a close relationship with the common iliac vessels and the sacral bone. A Laparotomy procedure revealed that the tumour was an irresectable mass. Neo-adjuvant radiotherapy (40 Gy) was administered in order to downsize the tumour. Six weeks later a new CT-scan revealed a major reduction of the tumour, which enabled a successful radical resection of the tumour to be performed. Histopathological analysis of the tumour showed the hyaline vascular type of CD.
Conclusions
Neo-adjuvant radiotherapy should be considered in case of an irresectable unicentric CD.
doi:10.1186/1748-717X-5-7
PMCID: PMC2827478  PMID: 20122250
7.  NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial) 
Background
Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer.
Methods/design
Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).
Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy).
Discussion
The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice.
Trial registration
ISRCTN45750457
doi:10.1186/1756-6649-8-3
PMCID: PMC3301128  PMID: 18671847
8.  Clinical management of women with metastatic breast cancer: a descriptive study according to age group 
BMC Cancer  2006;6:179.
Background
The primary aim of treatment of a patient who has developed metastatic disease is palliation. The objectives of the current study are to describe and quantify the clinical management of women with metastatic breast cancer from the diagnosis of metastatic disease until death and to analyze differences between age groups.
Methods
Data were collected from the medical files of all patients (n = 116) who had died after December 31, 1999, after a diagnosis of metastatic breast cancer in two teaching hospitals in the south of the Netherlands.
Results
Of the 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after the diagnosis of localized breast cancer. Before they died, 70% of the 116 patients developed metastases in one or more bones, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin. Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. Seventy-seven (66%) of the 116 patients with metastatic breast cancer received chemotherapy. This proportion decreased with age (p = 0.005), as did the number of schemes per patient. Together, they received 132 chemotherapy schemes, of which 35 (27%) resulted in partial remission or stabilization of the disease process. Ninety-eight patients (84%) received hormonal treatment. This proportion did not differ between the three age groups. Together, they received 216 hormonal treatments, 38 (16%) of which resulted in partial remission or stabilization of the disease process. Seventy-nine patients (68%) received palliative radiotherapy. This proportion decreased with age (p = 0.03). Together, they underwent 216 courses, 176 (77%) of which resulted in relief of the complaints.
Conclusion
Patients aged 70 years and older are less likely to receive chemotherapy or radiotherapy. Part of this difference could be explained by their shorter survival time after the diagnosis of metastatic disease and their lower risk of developing brain and bone metastases. However, more research is needed to understand the age-related differences in the treatment of metastatic breast cancer, and especially how comorbidity and frailty limit therapeutic choices.
doi:10.1186/1471-2407-6-179
PMCID: PMC1534056  PMID: 16824210

Results 1-8 (8)